Deep RNA sequencing of muscle tissue reveals absence of viral signatures in dermatomyositis

Authors

  • Victor M. Corman Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, 10117 Berlin, Germany and German Centre for Infection Research (DZIF), Partner Site Berlin, Charitéplatz 1, 10117 Berlin, Germany
  • Corinna Preusse Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, 10117 Berlin, Germany
  • Julia Melchert Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, 10117 Berlin, Germany and German Centre for Infection Research (DZIF), Partner Site Berlin, Charitéplatz 1, 10117 Berlin, Germany
  • Olivier Benveniste Department of Internal Medicine and Clinical Immunology, Pitié-Salpêtrière University Hospital, 75013 Paris, France
  • Randi Koll Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, 10117 Berlin, Germany
  • Hans-Hilmar Goebel Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, 10117 Berlin, Germany
  • Terry C. Jones Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, 10117 Berlin, Germany and German Centre for Infection Research (DZIF), Partner Site Berlin, Charitéplatz 1, 10117 Berlin, Germany; Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
  • Christian Drosten Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, 10117 Berlin, Germany and German Centre for Infection Research (DZIF), Partner Site Berlin, Charitéplatz 1, 10117 Berlin, Germany
  • Ulrike Schara-Schmidt Department of Pediatric Neurology and Centre for Neuromuscular Disorders in children and adolescents, Center for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany
  • Sarah Leonard-Louis Department of Neuropathology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, INSERM, Hôpital Pitié-Salpêtrière, France
  • Werner Stenzel Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, 10117 Berlin, Germany
  • Josefine Radke Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, 10117 Berlin, Germany; Institute of Pathology, Universitätsmedizin Greifswald, Greifswald, Germany https://orcid.org/0000-0001-9860-2007

DOI:

https://doi.org/10.17879/freeneuropathology-2024-5149

Keywords:

Dermatomyositis (DM), Interferon (IFN), Viral signature, Next generation sequencing

Abstract

Objective: To explore a possible connection between active viral infections and manifestation of Dermatomyositis (DM).

Methods: Skeletal muscle biopsies were analyzed from patients diagnosed with juvenile (n=10) and adult (n=12) DM. Adult DM patients harbored autoantibodies against either TIF-1γ (n=7) or MDA5 (n=5). Additionally, we investigated skeletal muscle biopsies from non-diseased controls (NDC, n=5). We used an unbiased high-throughput sequencing (HTS) approach to detect viral sequences. To further increase sequencing depth, a host depletion approach was applied.

Results: In this observational study, no relevant viral sequences were detected either by native sequencing or after host depletion. The absence of detectable viral sequences makes an active viral infection of the muscle tissue unlikely to be the cause of DM in our cohorts.

Discussion: Type I interferons (IFN) play a major role in the pathogenesis of both juvenile and adult dermatomyositis (DM). The IFN response is remarkably conserved between DM subtypes classified by specific autoantibodies. Certain acute viral infections are accompanied by a prominent type I IFN response involving similar downstream mechanisms as in DM. Aiming to elucidate the pathogenesis of DM in skeletal muscle tissue, we used an untargeted high-throughput sequencing and a host depletion approach to detect possible causative viruses.

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Published

2024-01-04

How to Cite

Corman, V. M., Preusse, C., Melchert, J., Benveniste, O., Koll, R., Goebel, H.-H., Jones, T. C., Drosten, C., Schara-Schmidt, U., Leonard-Louis, S., Stenzel, W., & Radke, J. (2024). Deep RNA sequencing of muscle tissue reveals absence of viral signatures in dermatomyositis. Free Neuropathology, 5, 1. https://doi.org/10.17879/freeneuropathology-2024-5149

Issue

Vol. 5 (2024)

Section

Original Papers

License

Copyright (c) 2023 Victor M. Corman, Corinna Preusse, Julia Melchert, Olivier Benveniste, Randi Koll, Hans-Hilmar Goebel, Terry C. Jones, Christian Drosten, Ulrike Schara-Schmidt, Sarah Leonard-Louis, Werner Stenzel, Josefine Radke

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Papers are published open access under the Creative Commons BY 4.0 license. This license lets others distribute, remix, adapt, and build upon your work, even commercially, as long as they credit you for the original creation. Data included in the article are made available under the CC0 1.0 Public Domain Dedication waiver, unless otherwise stated, meaning that all copyrights are waived.